Patients with partial coronary artery obstruction ranging from 60-95 percent, many of whom are symptom free, often die suddenly, without autopsy evidence of ante mortem fibrin thrombus formation, or other acute exacerbation of their disease. Transient acute platelet thrombus formation in the area of stenosis is now postulated to be a cause of sudden coronary death, and large groups of patients are now taking platelet inhibitors in an effort to reduce this risk. We propose to use an established animal model in which platelet thrombi form in stenosed coronary and other stenosed arteries. This model can be used on a variety of animals including sub human primates. We will examine these thrombi which can form within five to ten minutes and, if not treated, can reduce coronary flow producing arrhythmias and sudden death. We will do light, immunofluorescence, and scanning electron microscopy on these acutely forming thrombi to determine their composition and morphology, which may well be different from that of thrombi that are several hours in forming. In addition, we will use fluorescein conjugated antisera to dog red cells and fibrin to determine their contribution to the thrombus formation. We will also obtain acute thrombi which occur in patients at the time of cardiac catheterization and these will be processed the same as the animal thrombi. We will compare the ultrastructural composition and note the differences and similarities of human and dog acute thrombi. We will pursue our recent findings that red cells may play an active role in the formation of these acute thrombi and continue to study agents which appear to reduce this red cell involvement. We will also try to determine why 15-20 percent of the dogs, pigs, rabbits and monkeys studied with our model seem to have a protective mechanism and do not form fatal thrombi. This may suggest a new previously unknown concept for protecting patients with vascular disease. This model provides an ideal way to study agents which may inhibit this thrombus formation, and may thus be beneficial to patients with diseased arteries.